PDF(Pubmed)
Abstract：
Although the majority of patients with chronic myeloid leukemia (CML) enjoy an excellent prognosis tyrosine kinase inhibitor (TKI) therapy, resistance remains a significant clinical problem. Resistance can arise from mutations in the kinase domain of ABL preventing drug binding, or due to ill-defined kinase-independent mechanisms. In this case report, we describe the case of a 27-year-old woman with a long-standing history of chronic phase (CP) CML who developed kinase-independent resistance with mutations in ASXL1 and RUNX1. As a consequence of uncontrolled disease, she progressed to a chronic myelomonocytic leukemia-like (CMML) accelerated phase (AP) disease with the acquisition of a mutation in IDH1. This disease progression was associated with the development of an inflammatory serositis, a phenomenon that has been described in CMML but not in AP-CML. This case presents key features of kinase-independent resistance with insight into potential mechanisms, highlights management challenges, and describes a novel systemic inflammatory response that occurred in this patient upon disease progression.
摘要：
尽管大多数慢性粒细胞白血病（CML）患者享有良好的预后酪氨酸激酶抑制剂（TKI）治疗，耐药性仍然是一个重要的临床问题。耐药性可由ABL激酶结构域的突变引起，阻止药物结合，或由于不明确的激酶独立机制。在这个案例报告中,我们描述了一例27岁女性的病例,该女性长期有慢性期(CP)CML病史,出现了ASXL1和RUNX1突变的激酶非依赖性耐药.由于不受控制的疾病，她进展为慢性粒单核细胞白血病样(CMML)加速期(AP)疾病,并获得IDH1突变.这种疾病进展与炎症性浆膜炎的发展有关，一种在CMML中描述但在AP-CML中没有描述的现象。这个案例展示了激酶非依赖性耐药性的关键特征，并深入了解了潜在的机制。突出了管理挑战，并描述了该患者在疾病进展时发生的新型全身性炎症反应。
